Crystal Structure of Steroid Reductase SRD5A Reveals Conserved Steroid Reduction Mechanism
July 2020
in “
bioRxiv (Cold Spring Harbor Laboratory)
”
Studysummary This study reports that structural and biochemical analysis of steroid 5α-reductases clarifies how they mediate steroid reduction with NADPH, potentially aiding in designing targeted therapies. Our plain-language summary of this paper — not a Tressless recommendation.
The study reported the crystal structure of the steroid 5α-reductase (SRD5A) from Proteobacteria bacterium, revealing a conserved mechanism for NADPH-mediated steroid reduction. The structure, resolved at 2.0 Å, showed that PbSRD5A, which shares significant sequence similarity with human SRD5A1 and SRD5A2, exists as a monomer with seven transmembrane segments. These segments form a hydrophobic cavity for steroid binding and coordinate with NADPH through hydrogen bonds. The findings provided insights into substrate recognition and could aid in designing specific therapeutic molecules targeting SRD5As to treat conditions like benign prostatic hyperplasia, alopecia, prostatic cancer, and infertility.